RESUMO
The aim of the present study is to synthesize Cu1-xSrxS (x = 0.00, 0.025, 0.05, 0.075, and 0.1) nanoparticles (NPs) using an easy chemical co-precipitation method in an efficient, inexpensive, and simple technique. The structural, morphological, and optical properties of the prepared samples were investigated using XRD, TEM, XRF, UV-Vis DRS, and PL characterization techniques. XRD spectra confirmed the Sr-doped copper sulfide nanoparticles have a hexagonal structure with crystallite sizes ranging from 15.15 to 16.04 nm, and, by XRF, the presence of the dopant was detected. TEM analysis confirmed that strontium ions had an effect on the shape of the CuS nanostructure, and the particle size increased from 16.27 to 17.32 nm after doping. A study using UV-Vis showed the presence of Sr doping increased the optical energy band gap (1.38 eV to 1.59 eV). At room temperature, one photoluminescence (PL) band was found at 826 nm. The antibacterial activity of CuS nanostructures against E. coli, P. aeruginosa, Klebsiella pneumonia, and S. aureus was evaluated by zone of inhibition. Sr doped CuS NPs exhibited the highest antibacterial activity against S. aureus (17 to 29 mm). Also, the results demonstrated that samples doped with 5, 7.5, and 10% Sr exhibited inhibitory effects against all the tested microbial strains higher than the antibiotic.
Assuntos
Antibacterianos , Cobre , Nanoestruturas , Estrôncio , Antibacterianos/farmacologia , Antibacterianos/química , Cobre/química , Cobre/farmacologia , Estrôncio/química , Estrôncio/farmacologia , Nanoestruturas/química , Testes de Sensibilidade Microbiana , Escherichia coli/efeitos dos fármacos , Tamanho da Partícula , Klebsiella pneumoniae/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Difração de Raios X , Staphylococcus aureus/efeitos dos fármacos , Bactérias/efeitos dos fármacosRESUMO
Bone defect repair and postoperative infections are among the most challenging issues faced by orthopedic surgeons. Thus, the antibacterial agent Cu and the osteogenic promoter Sr have been widely incorporated into biodegradable alloys separately. However, to the best of our knowledge, the synergistic effects of Cu and Sr on zinc alloys have not been investigated. Therefore, we have developed a series of novel Zn-4Cu-xSr (x = 0.05, 0.1, and 0.3 wt %) alloys. Our results showed that the addition of Cu and Sr significantly increased the strength of pure zinc while maintaining a certain level of ductility. Plastic deformation further enhanced the strength and ductility of the alloys. The tensile strength of HR Zn-4Cu-xSr alloys remains between 233.34 ± 1.31 MPa and 235.81 ± 3.0 MPa, with elongation values ranging from 45.7 ± 1.56% to 49.6 ± 6.22%. The HE Zn-4Cu-0.05Sr alloy exhibits a high elongation of 95.05 ± 11.1%. Furthermore, the HE Zn-4Cu-0.1Sr alloy demonstrates the best overall mechanical performance with ultimate tensile strength (σuts), yield strength (σys), and elongation (ε) values of 252.73 ± 0.12 MPa, 181.0 ± 0.79 MPa, and 42.8 ± 1.13%, respectively. The corrosion rate of HE Zn-4Cu-xSr alloys increases with an increase in Sr content. All samples exhibit satisfactory cytocompatibility with the cells displaying a healthy spindle-like morphology. In vitro antibacterial tests show that the HE Zn-4Cu-xSr alloys exhibit significant antibacterial effects against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), with the antibacterial properties strengthening as the Sr content increases. Therefore, this study demonstrates the tremendous potential application of Zn-4Cu-xSr alloys in biodegradable zinc alloys for bone fracture fixation and repair.
Assuntos
Ligas , Cobre , Estrôncio , Resistência à Tração , Zinco , Ligas/química , Ligas/farmacologia , Zinco/química , Zinco/farmacologia , Cobre/química , Cobre/farmacologia , Estrôncio/química , Estrôncio/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Teste de Materiais , Humanos , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacosRESUMO
OBJECTIVES: This study aimed to investigate the osseointegration of titanium (Ti) implants with micro-nano textured surfaces functionalized with strontium additions (Sr) in a pre-clinical rat tibia model. METHODOLOGY: Ti commercially pure (cp-Ti) implants were installed bilaterally in the tibia of 64 Holtzman rats, divided into four experimental groups (n=16/group): (1) Machined surface - control (C); (2) Micro-nano textured surface treatment (MN); (3) Micro-nano textured surface with Sr2+ addition (MNSr); and (4) Micro-nano textured surface with a higher complementary addition of Sr2+ (MNSr+). In total, two experimental euthanasia periods were assessed at 15 and 45 days (n=8/period). The tibia was subjected to micro-computed tomography (µ-CT), histomorphometry with the EXAKT system, removal torque (TR) testing, and gene expression analysis by PCR-Array of 84 osteogenic markers. Gene expression and protein production of bone markers were performed in an in vitro model with MC3T3-E1 cells. The surface characteristics of the implants were evaluated by scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), and laser scanning confocal microscopy. RESULTS: SEM, confocal, and EDS analyses demonstrated the formation of uniform micro-nano textured surfaces in the MN group and Sr addition in the MNSr and MNSr+ groups. TR test indicated greater osseointegration in the 45-day period for treated surfaces. Histological analysis highlighted the benefits of the treatments, especially in cortical bone, in which an increase in bone-implant contact was found in groups MN (15 days) and MNSr (45 days) compared to the control group. Gene expression analysis of osteogenic activity markers showed modulation of various osteogenesis-related genes. According to the in vitro model, RT-qPCR and ELISA demonstrated that the treatments favored gene expression and production of osteoblastic differentiation markers. CONCLUSIONS: Micro-nano textured surface and Sr addition can effectively improve and accelerate implant osseointegration and is, therefore, an attractive approach to modifying titanium implant surfaces with significant potential in clinical practice.
Assuntos
Implantes Dentários , Osseointegração , Estrôncio , Propriedades de Superfície , Tíbia , Titânio , Microtomografia por Raio-X , Titânio/química , Osseointegração/efeitos dos fármacos , Animais , Estrôncio/farmacologia , Estrôncio/química , Fatores de Tempo , Tíbia/efeitos dos fármacos , Tíbia/cirurgia , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Teste de Materiais , Masculino , Osteogênese/efeitos dos fármacos , Microscopia Eletrônica de Varredura , Camundongos , Torque , Expressão Gênica/efeitos dos fármacos , Análise de Variância , Reação em Cadeia da Polimerase em Tempo Real , Ratos , Nanoestruturas , Valores de ReferênciaRESUMO
Despite the numerous studies on biocompatibility with nano-biomaterials, the biological effects of strontium-substituted HA nanoparticles (nSrHA) need to be better understood. So, we conducted an embryotoxicity test using zebrafish (Danio rerio) according to the OECD 236 guideline, a model that represents a viable alternative that bridges the gap between in vitro and mammalian models. Zebrafish embryos were exposed for 120 h to microspheres containing nSrHA nanoparticles with low and high crystallinity, synthesized at temperatures of 5°C (nSrHA5) and 90°C (nSrHA90). We evaluated lethality, developmental parameters, and reactive oxygen species (ROS) production. The larval behavior was assessed at 168 hpf to determine if the biomaterials affected motor responses and anxiety-like behavior. The results showed that the survival rate decreased significantly for the nSrHA5 group (low crystalline particles), and an increase in ROS was also observed in this group. However, none of the biomaterials caused morphological changes indicative of toxicity during larval development. Additionally, the behavioral tests did not reveal any alterations in all experimental groups, indicating the absence of neurotoxic effects from exposure to the tested biomaterials. These findings provide valuable insights into the biosafety of modified HA-based nanostructured biomaterials, making them a promising strategy for bone tissue repair. As the use of hydroxyapatite-based biomaterials continues to grow, it is crucial to ensure rigorous control over the quality, reliability, and traceability of these materials.
Assuntos
Estrôncio , Peixe-Zebra , Animais , Estrôncio/química , Estrôncio/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Embrião não Mamífero/efeitos dos fármacos , Teste de Materiais , Hidroxiapatitas/química , Hidroxiapatitas/farmacologia , Nanoestruturas/química , Larva/efeitos dos fármacosRESUMO
BACKGROUND: Calcium silicate-based bioceramics have been applied in endodontics as advantageous materials for years, many chemical components and new synthesizing methods were used to improve the base formulation of the materials for positively affecting the sealers properties. Recently, a novel biomaterial formulation, grounded in strontium silicate, has been introduced to the market, offering potential advancements in the field. OBJECTIVE: To comparatively analyze the cytotoxicity and cell migration effects of a novel strontium silicate-based bioceramic material (CRoot SP) and those of calcium silicate-based (iRoot SP) and epoxide amine resin (AH Plus) sealers on stem cells derived from rat apical papilla(rSCAPs). METHODS: rSCAPs were isolated and characterized in vitro and subsequently cultured in the presence of various concentrations of CRoot SP, iRoot SP and AH Plus extracts. Cytotoxicity was assessed by CCK-8 assay, and cell-migration capacity was assessed by using wound healing assays . RESULTS: No significant differences in cell viability were observed in the 0.02 mg/mL and 0.2 mg/mL sealer groups. The cell viability of CRoot SP was consistently greater than that of iRoot SP at concentrations of 5 mg/mL and 10 mg/mL across all time points. Maximum cytotoxic effect was noted on day 5 with 10 mg/mL AH Plus.The scratch was partly healed by cell migration in all groups at 24 h, and the 0.02 mg/mL, and 0.2 mg/mL CRoot SP exerted beneficial effects on rSCAPs migration. CONCLUSIONS: CRoot SP exhibited less cytotoxic than the iRoot SP and AH Plus extracts after setting. A lower concentration of CRoot SP thus promotes the cell migration capacity of rSCAPs, and it may achieve better tissue repair during root canal treatment.
Assuntos
Compostos de Cálcio , Movimento Celular , Sobrevivência Celular , Resinas Epóxi , Materiais Restauradores do Canal Radicular , Silicatos , Células-Tronco , Animais , Silicatos/farmacologia , Movimento Celular/efeitos dos fármacos , Materiais Restauradores do Canal Radicular/farmacologia , Materiais Restauradores do Canal Radicular/toxicidade , Ratos , Compostos de Cálcio/farmacologia , Resinas Epóxi/farmacologia , Resinas Epóxi/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Técnicas In Vitro , Teste de Materiais , Células Cultivadas , Cerâmica/farmacologia , Estrôncio/farmacologia , Papila Dentária/citologia , Papila Dentária/efeitos dos fármacos , Ápice Dentário/efeitos dos fármacos , Ápice Dentário/citologiaRESUMO
One way to effectively address endophyte infection and loosening is the creation of multifunctional coatings that combine anti-inflammatory, antibacterial, and vascularized osteogenesis. This study started with the preparation of strontium-doped titanium dioxide nanotubes (STN) on the titanium surface. Next, tannic acid (TA), gentamicin sulfate (GS), and pluronic F127 (PF127) were successfully loaded into the STN via layer-by-layer self-assembly, resulting in the STN@TA-GS/PF composite coatings. The findings demonstrated the excellent hydrophilicity and bioactivity of the STN@TA-GS/PF coating. STN@TA-GS/PF inhibited E. coli and S. aureus in vitro to a degree of roughly 80.95â¯% and 92.45â¯%, respectively. Cellular investigations revealed that on the STN@TA-GS/PF surface, the immune-system-related RAW264.7, the vasculogenic HUVEC, and the osteogenic MC3T3-E1 showed good adhesion and proliferation activities. STN@TA-GS/PF may influence RAW264.7 polarization toward the M2-type and encourage MC3T3-E1 differentiation toward osteogenesis at the molecular level. Meanwhile, the STN@TA-GS/PF coating achieved effective removal of ROS within HUVEC and significantly promoted angiogenesis. In both infected and non-infected bone defect models, the STN@TA-GS/PF material demonstrated strong anti-inflammatory, antibacterial, and vascularization-promoting osteogenesis properties. In addition, STN@TA-GS/PF had good hemocompatibility and biosafety. The three-step process used in this study to modify the titanium surface for several purposes gave rise to a novel concept for the clinical design of antimicrobial coatings with immunomodulatory properties.
Assuntos
Antibacterianos , Anti-Inflamatórios , Materiais Revestidos Biocompatíveis , Escherichia coli , Nanotubos , Próteses e Implantes , Staphylococcus aureus , Estrôncio , Titânio , Titânio/química , Titânio/farmacologia , Nanotubos/química , Camundongos , Animais , Estrôncio/química , Estrôncio/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Staphylococcus aureus/efeitos dos fármacos , Humanos , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Escherichia coli/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Células RAW 264.7 , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Propriedades de Superfície , Taninos/química , Taninos/farmacologia , Osteogênese/efeitos dos fármacos , Poloxâmero/química , Poloxâmero/farmacologia , Proliferação de Células/efeitos dos fármacos , Gentamicinas/farmacologia , Gentamicinas/química , Tamanho da PartículaRESUMO
Endowing titanium surfaces with multifunctional properties can reduce implant-related infections and enhance osseointegration. In this study, titanium dioxide nanotubes with strontium doping (STN) were first created on the titanium surface using anodic oxidation and hydrothermal synthesis techniques. Next, casein phosphopeptide (CCP) and an antimicrobial peptide (HHC36) were loaded into the STN with the aid of vacuum physical adsorption (STN-CP-H), giving the titanium surface a dual function of "antimicrobial-osteogenic". The surface of STN-CP-H has a suitable roughness and good hydrophilicity, which is conducive to osteoblasts. STN-CP-H had a 99 % antibacterial rate against S. aureus and E. coli and effectively prevented the growth of bacterial biofilm. Meanwhile, the antibacterial mechanism of STN-CP-H was initially explored with the help of transcriptome sequencing technology. STN-CP-H could greatly increase osteoblast adhesion, proliferation, and expression of osteogenic markers (alkaline phosphatase, runt-related transcription) when CCP and Sr worked together synergistically. In vivo, the STN-CP-H coating could effectively promote new osteogenesis around titanium implant bone and had no toxic effects on heart, liver, spleen, lung and kidney tissues. A potential anti-infection bone healing material, STN-CP-H bifunctional coating developed in this work efficiently inhibited bacterial infection of titanium implants and encouraged early osseointegration.
Assuntos
Peptídeos Antimicrobianos , Caseínas , Nanotubos , Estrôncio , Titânio , Titânio/química , Titânio/farmacologia , Nanotubos/química , Animais , Caseínas/química , Caseínas/farmacologia , Estrôncio/química , Estrôncio/farmacologia , Peptídeos Antimicrobianos/química , Peptídeos Antimicrobianos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Osteogênese/efeitos dos fármacos , Fosfopeptídeos/química , Fosfopeptídeos/farmacologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Camundongos , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Osseointegração/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , CoelhosRESUMO
Bone tissue engineering offers a promising alternative to stimulate the regeneration of damaged tissue, overcoming the limitations of conventional autografts and allografts. Recently, titanium alloy (Ti) implants have garnered significant attention for treating critical-sized bone defects, especially with the advancement of 3D printing technology. Although Ti alloys have impressive versatility, their lack of cellular adhesion, osteogenic and antibacterial properties are significant factors that contribute to their failure. Hence, to overcome these obstacles, this study aimed to incorporate osteoinductive and antibacterial cue-loaded hydrogels into 3D-printed Ti (3D-Ti) scaffolds. 3D-Ti scaffolds were synthesized using the direct metal laser sintering method and loaded with a gelatin (Gel) hydrogel containing strontium-doped silver nanoparticles (Sr-Ag NPs). Compared with Ag NPs, Sr-doped Ag NPs increased the expression of Runx2 mRNA, which is a key bone transcription factor. We subjected the bioactive 3D-hybrid scaffolds (3D-Ti/Gel/Sr-Ag NPs) to physicochemical and material characterization, followed by cytocompatibility and osteogenic evaluation. The microporous and macroporous topographies of the scaffolds with Sr-Ag NPs showed increased Runx2 expression and matrix mineralization, with potent antibacterial properties. Therefore, the 3D-Ti scaffolds incorporated with Sr-Ag NP-loaded Gel hydrogels favored osteoblast differentiation and antibacterial activity, indicating their potential for orthopedic applications.
Assuntos
Antibacterianos , Diferenciação Celular , Gelatina , Hidrogéis , Nanopartículas Metálicas , Osteoblastos , Osteogênese , Impressão Tridimensional , Prata , Estrôncio , Engenharia Tecidual , Alicerces Teciduais , Titânio , Prata/química , Prata/farmacologia , Gelatina/química , Estrôncio/química , Estrôncio/farmacologia , Titânio/química , Titânio/farmacologia , Engenharia Tecidual/métodos , Osteoblastos/efeitos dos fármacos , Osteoblastos/citologia , Antibacterianos/química , Antibacterianos/farmacologia , Alicerces Teciduais/química , Hidrogéis/química , Hidrogéis/farmacologia , Nanopartículas Metálicas/química , Diferenciação Celular/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Animais , Camundongos , Osso e Ossos/efeitos dos fármacosRESUMO
Mesoporous bioactive glass nanoparticles (MBGNs) doped with therapeutical ions present multifunctional systems that enable a synergistic outcome through the dual delivery of drugs and ions. The aim of this study was to evaluate influence of co-doping with strontium and magnesium ions (SrMg-MBGNs) on the properties of MBGNs. A modified microemulsion-assisted sol-gel synthesis was used to obtain particles, and their physicochemical properties, bioactivity, and drug-loading/release ability were evaluated. Indirect biological assays using 2D and 3D cell culture models on human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and endothelial EA.hy926 cells, respectively, were used to determine biocompatibility of MBGNs, their influence on alkaline phosphatase (ALP) production, calcium deposition, and cytoskeletal organization. Results showed that Sr,Mg-doping increased pore volume and solubility, and changed the mesoporous structure from worm-like to radial-dendritic, which led to a slightly accelerated drug release compared to pristine MBGNs. Biological assays confirmed that particles are biocompatible, and have ability to slightly induce ALP production and calcium deposition of hBM-MSCs, as well as to significantly improve the proliferation of EA.hy926 compared to biochemical stimulation via vascular endothelial growth factor (VEGF) administration or regular media. Fluorescence staining revealed that SrMg-MBGNs had a similar effect on EA.hy926 cytoskeletal organization to the VEGF group. In conclusion, Sr,Mg-MBGNs might be considered promising biomaterial for biomedical applications.
Assuntos
Regeneração Óssea , Sistemas de Liberação de Medicamentos , Vidro , Magnésio , Células-Tronco Mesenquimais , Nanopartículas , Estrôncio , Humanos , Regeneração Óssea/efeitos dos fármacos , Nanopartículas/química , Estrôncio/química , Estrôncio/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Porosidade , Magnésio/química , Vidro/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Linhagem Celular , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Proliferação de Células/efeitos dos fármacosRESUMO
Purpose: Functional inorganic nanomaterials (NMs) are widely exploited as bioactive materials and drug depots. The lack of a stable form of application of NMs at the site of skin injury, may impede the removal of the debridement, elevate pH, induce tissue toxicity, and limit their use in skin repair. This necessitates the advent of innovative wound dressings that overcome the above limitations. The overarching objective of this study was to exploit strontium-doped mesoporous silicon particles (PSiSr) to impart multifunctionality to poly(lactic-co-glycolic acid)/gelatin (PG)-based fibrous dressings (PG@PSiSr) for excisional wound management. Methods: Mesoporous silicon particles (PSi) and PSiSr were synthesized using a chemo-synthetic approach. Both PSi and PSiSr were incorporated into PG fibers using electrospinning. A series of structure, morphology, pore size distribution, and cumulative pH studies on the PG@PSi and PG@PSiSr membranes were performed. Cytocompatibility, hemocompatibility, transwell migration, scratch wound healing, and delineated angiogenic properties of these composite dressings were tested in vitro. The biocompatibility of composite dressings in vivo was assessed by a subcutaneous implantation model of rats, while their potential for wound healing was discerned by implantation in a full-thickness excisional defect model of rats. Results: The PG@PSiSr membranes can afford the sustained release of silicon ions (Si4+) and strontium ions (Sr2+) for up to 192 h as well as remarkably promote human umbilical vein endothelial cells (HUVECs) and NIH-3T3 fibroblasts migration. The PG@PSiSr membranes also showed better cytocompatibility, hemocompatibility, and significant formation of tubule-like networks of HUVECs in vitro. Moreover, PG@PSiSr membranes also facilitated the infiltration of host cells and promoted the deposition of collagen while reducing the accumulation of inflammatory cells in a subcutaneous implantation model in rats as assessed for up to day 14. Further evaluation of membranes transplanted in a full-thickness excisional wound model in rats showed rapid wound closure (PG@SiSr vs control, 96.1% vs 71.7%), re-epithelialization, and less inflammatory response alongside skin appendages formation (eg, blood vessels, glands, hair follicles, etc.). Conclusion: To sum up, we successfully fabricated PSiSr particles and prepared PG@PSiSr dressings using electrospinning. The PSiSr-mediated release of therapeutic ions, such as Si4+ and Sr2+, may improve the functionality of PLGA/Gel dressings for an effective wound repair, which may also have implications for the other soft tissue repair disciplines.
Assuntos
Bandagens , Gelatina , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Silício , Pele , Estrôncio , Cicatrização , Gelatina/química , Animais , Estrôncio/química , Estrôncio/farmacologia , Cicatrização/efeitos dos fármacos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Pele/efeitos dos fármacos , Porosidade , Ratos , Humanos , Silício/química , Ratos Sprague-Dawley , Camundongos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Masculino , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologiaRESUMO
Acrylic resins are widely used as the main components in removable orthodontic appliances. However, poor oral hygiene and maintenance of orthodontic appliances provide a suitable environment for the growth of pathogenic microorganisms. In this study, strontium-modified phosphate-based glass (Sr-PBG) was added to orthodontic acrylic resin at 0% (control), 3.75%, 7.5%, and 15% by weight to evaluate the surface and physicochemical properties of the novel material and its in vitro antifungal effect against Candida albicans (C. albicans). Surface microhardness and contact angle did not vary between the control and 3.75% Sr-PBG groups (p > 0.05), and the flexural strength was lower in the experimental groups than in the control group (p < 0.05), but no difference was found with Sr-PBG content (p > 0.05). All experimental groups showed an antifungal effect at 24 and 48 h compared to that in the control group (p < 0.05). This study demonstrated that 3.75% Sr-PBG exhibits antifungal effects against C. albicans along with suitable physicochemical properties, which may help to minimize the risk of adverse effects associated with harmful microbial living on removable orthodontic appliances and promote the use of various materials.
Assuntos
Resinas Acrílicas , Antifúngicos , Candida albicans , Vidro , Teste de Materiais , Fosfatos , Estrôncio , Propriedades de Superfície , Candida albicans/efeitos dos fármacos , Resinas Acrílicas/química , Estrôncio/farmacologia , Estrôncio/química , Antifúngicos/farmacologia , Vidro/química , Fosfatos/farmacologia , Polimerização , Dureza , Resistência à Flexão , Humanos , Técnicas In VitroRESUMO
This study aimed to compare the biological properties of newly synthesized cements based on calcium phosphate with a commercially used cement, mineral trioxide aggregate (MTA). Strontium (Sr)-, Copper (Cu)-, and Zinc (Zn)-doped hydroxyapatite (miHAp) powder was obtained through hydrothermal synthesis and characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and energy dispersive X-ray spectrometry (EDX). Calcium phosphate cement (CPC) was produced by mixing miHAp powder with a 20 wt.% citric acid solution, followed by the assessment of its compressive strength, setting time, and in vitro bioactivity. Acetylsalicylic acid (ASA) was added to the CPC, resulting in CPCA. Biological tests were conducted on CPC, CPCA, and MTA. The biocompatibility of the cement extracts was evaluated in vitro using human dental pulp stem cells (hDPSCs) and in vivo using a zebrafish model. Antibiofilm and antimicrobial effect (quantified by CFUs/mL) were assessed against Streptococcus mutans and Lactobacillus rhamnosus. None of the tested materials showed toxicity, while CPCA even increased hDPSCs proliferation. CPCA showed a better safety profile than MTA and CPC, and no toxic or immunomodulatory effects on the zebrafish model. CPCA exhibited similar antibiofilm effects against S. mutans and L. rhamnosus to MTA.
Assuntos
Aspirina , Fosfatos de Cálcio , Cobre , Estrôncio , Zinco , Estrôncio/química , Estrôncio/farmacologia , Fosfatos de Cálcio/química , Fosfatos de Cálcio/farmacologia , Humanos , Animais , Aspirina/farmacologia , Aspirina/química , Cobre/química , Zinco/química , Zinco/farmacologia , Cimentos Dentários/química , Cimentos Dentários/farmacologia , Biofilmes/efeitos dos fármacos , Teste de Materiais , Peixe-Zebra , Polpa Dentária/citologia , Polpa Dentária/efeitos dos fármacos , Streptococcus mutans/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Difração de Raios X , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Proliferação de Células/efeitos dos fármacosRESUMO
Biodegradable metals, including magnesium, iron, and zinc alloys, have attracted extensive attention due to their good biodegradability and biocompatibility. However, the mechanical properties and corrosion rates of most biodegradable metallic materials have not yet reached the ideal level required for clinical applications. Strontium, as an element of Group IIA in the periodic table of elements, has similar chemical and biological properties to calcium. It can promote bone tissue development and increase bone strength. In addition, strontium can also promote angiogenesis and facilitate the repair of infarcted heart activity. Thus, strontium is commonly used as one of the most alloying elements to improve the in vitro and in vivo properties of biodegradable metals. Besides, strontium is also widely used in various bioactive coatings to improve the comprehensive properties of biodegradable metals. This paper outlines the role of strontium in the human body and summarizes recent research and applications of strontium-containing biodegradable metallic materials. Finally, this paper also provides an outlook on the challenges faced in applying and researching strontium in biodegradable metals.
Assuntos
Materiais Biocompatíveis , Estrôncio , Estrôncio/química , Estrôncio/farmacologia , Humanos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Animais , Metais/químicaRESUMO
Bone defects, resulting from trauma, inflammation, tumors, and various other factors, affect both health and quality of life. Although autologous bone transplantation is the gold-standard treatment for bone defects, it has disadvantages such as donor site limitations, prolonged surgical durations, and potential complications, necessitating the development of alternative bone tissue engineering materials. In this study, we used 3D printing technology to fabricate porous titanium implants characterized by superior biocompatibility and mechanical properties. Sodium alginate (SA) and strontium ions (Sr2+) were integrated into mineralized collagen matrices (MCs) to develop strontium-functionalized alginate-mineralized collagen hydrogels (SAMs) with high mechanical strength and sustained metal ion release ability. SAMs were seamlessly incorporated into the porous structures of 3D-printed titanium scaffolds, establishing a novel organic-inorganic bioactive interface. This composite system exhibited high biocompatibility in vitro and increased the expression of genes important for osteogenic differentiation and angiogenesis. In a rabbit model of femoral defect, the titanium implants effectively promoted bone and vascular regeneration on their surface, highlighting their potential in facilitating bone-implant integration.
Assuntos
Ligas , Colágeno , Hidrogéis , Osseointegração , Osteogênese , Impressão Tridimensional , Alicerces Teciduais , Titânio , Titânio/química , Animais , Osteogênese/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Alicerces Teciduais/química , Coelhos , Osseointegração/efeitos dos fármacos , Colágeno/química , Colágeno/farmacologia , Porosidade , Ligas/química , Ligas/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Estrôncio/química , Estrôncio/farmacologia , Engenharia Tecidual/métodos , Alginatos/química , Alginatos/farmacologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologiaRESUMO
Regenerating periodontal defects in osteoporosis patients presents a significant clinical challenge. Unlike the relatively straightforward regeneration of homogeneous bone tissue, periodontal regeneration requires the intricate reconstruction of the cementum-periodontal ligament-alveolar bone interface. Strontium (Sr)-doped biomaterials have been extensively utilized in bone tissue engineering due to their remarkable pro-osteogenic attributes. However, their application in periodontal tissue regeneration has been scarcely explored. In this study, we synthesized an innovative injectable Sr-BGN/GNM scaffold by integrating Sr-doped bioactive glass nanospheres (Sr-BGNs) into the nanofiber architecture of gelatin nanofiber microspheres (GNMs). This design, mimicking the natural bone extracellular matrix (ECM), enhanced the scaffold's mechanical properties and effectively controlled the sustained release of Sr ions (Sr2+), thereby promoting the proliferation, osteogenic differentiation, and ECM secretion of PDLSCs and BMSCs, as well as enhancing vascularization in endothelial cells. In vivo experiments further indicated that the Sr-BGNs/GNMs significantly promoted osteogenesis and angiogenesis. Moreover, the scaffold's tunable degradation kinetics optimized the prolonged release and pro-regenerative effects of Sr2+ in vivo, matching the pace of periodontal regeneration and thereby facilitating the regeneration of functional periodontal tissues under osteoporotic conditions. Therefore, Sr-BGNs/GNMs emerge as a promising candidate for advancing periodontal regeneration strategies.
Assuntos
Matriz Extracelular , Microesferas , Nanofibras , Osteoporose , Estrôncio , Estrôncio/química , Estrôncio/farmacologia , Nanofibras/química , Osteoporose/tratamento farmacológico , Humanos , Matriz Extracelular/química , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Animais , Osteogênese/efeitos dos fármacos , Alicerces Teciduais/química , Diferenciação Celular/efeitos dos fármacos , Engenharia Tecidual , Proliferação de Células/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Regeneração/efeitos dos fármacosRESUMO
Large bone defects resulting from fractures and diseases have become a significant medical concern, usually impeding spontaneous healing through the body's self-repair mechanism. Calcium phosphate (CaP) bioceramics are widely utilized for bone regeneration, owing to their exceptional biocompatibility and osteoconductivity. However, their bioactivities in repairing healing-impaired bone defects characterized by conditions such as ischemia and infection remain limited. Recently, an emerging bioceramics zinc-strontium phosphate (ZSP, Zn2Sr(PO4)2) has received increasing attention due to its remarkable antibacterial and angiogenic abilities, while its plausible biomedical utility on tissue regeneration is nonetheless few. In this study, gallic acid-grafted gelatin (GGA) with antioxidant properties was injected into hydrogels to scavenge reactive oxygen species and regulate bone microenvironment while simultaneously incorporating ZSP to form GGA-ZSP hydrogels. The GGA-ZSP hydrogel exhibits low swelling, and in vitro cell experiments have demonstrated its favorable biocompatibility, osteogenic induction potential, and ability to promote vascular regeneration. In an in vivo bone defect model, the GGA-ZSP hydrogel significantly enhanced the bone regeneration rates. This study demonstrated that the GGA-ZSP hydrogel has pretty environmentally friendly therapeutic effects in osteogenic differentiation and massive bone defect repair.
Assuntos
Regeneração Óssea , Ácido Gálico , Gelatina , Hidrogéis , Osteogênese , Ácido Gálico/química , Ácido Gálico/farmacologia , Regeneração Óssea/efeitos dos fármacos , Gelatina/química , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Osteogênese/efeitos dos fármacos , Fosfatos/química , Fosfatos/farmacologia , Estrôncio/química , Estrôncio/farmacologia , Zinco/química , Zinco/farmacologia , Camundongos , Humanos , Osso e Ossos/efeitos dos fármacos , Masculino , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologiaRESUMO
Strontium, cobalt, and manganese ions are present in the composition of bone and useful for bone metabolism, even when combined with calcium phosphate in the composition of biomaterials. Herein we explored the possibility to include these ions in the composition of apatitic materials prepared through the cementitious reaction between ion-substituted calcium phosphate dibasic dihydrate, CaHPO4·2H2O (DCPD) and tetracalcium phosphate, Ca4(PO4)2O (TTCP). The results of the chemical, structural, morphological and mechanical characterization indicate that cobalt and manganese exhibit a greater delaying effect than strontium (about 15 at.%) on the cementitious reaction, even though they are present in smaller amounts within the materials (about 0.8 and 4.5 at.%, respectively). Furthermore, the presence of the foreign ions in the apatitic materials leads to a slight reduction of porosity and to enhancement of compressive strength. The results of biological tests show that the presence of strontium and manganese, as well as calcium, in the apatitic materials cultured in direct contact with human mesenchymal stem cells (hMSCs) stimulates their viability and activity. In contrast, the apatitic material containing cobalt exhibits a lower metabolic activity. All the materials have a positive effect on the expression of Vascular Endothelial Growth Factor (VEGF) and Von Willebrand Factor (vWF). Moreover, the apatitic material containing strontium induces the most significant reduction in the differentiation of preosteoclasts into osteoclasts, demonstrating not only osteogenic and angiogenic properties, but also ability to regulate bone resorption.
Assuntos
Regeneração Óssea , Cobalto , Manganês , Células-Tronco Mesenquimais , Osteogênese , Estrôncio , Estrôncio/farmacologia , Estrôncio/química , Cobalto/química , Humanos , Osteogênese/efeitos dos fármacos , Manganês/química , Manganês/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Regeneração Óssea/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/química , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fosfatos de Cálcio/química , Fosfatos de Cálcio/farmacologia , Sobrevivência Celular/efeitos dos fármacos , AngiogêneseRESUMO
Cartilage tissue engineering holds great promise for efficient cartilage regeneration. However, early inflammatory reactions to seed cells and/or scaffolds impede this process. Consequently, managing inflammation is of paramount importance. Moreover, due to the body's restricted chondrogenic capacity, inducing cartilage regeneration becomes imperative. Thus, a controlled platform is essential to establish an anti-inflammatory microenvironment before initiating the cartilage regeneration process. In this study, we utilized fifth-generation polyamidoamine dendrimers (G5) as a vehicle for drugs to create composite nanoparticles known as G5-Dic/Sr. These nanoparticles were generated by surface modification with diclofenac (Dic), known for its potent anti-inflammatory effects, and encapsulating strontium (Sr), which effectively induces chondrogenesis, within the core. Our findings indicated that the G5-Dic/Sr nanoparticle exhibited selective Dic release during the initial 9 days and gradual Sr release from days 3 to 15. Subsequently, these nanoparticles were incorporated into a gelatin methacryloyl (GelMA) hydrogel, resulting in GelMA@G5-Dic/Sr. In vitro assessments demonstrated GelMA@G5-Dic/Sr's biocompatibility with bone marrow stem cells (BMSCs). The enclosed nanoparticles effectively mitigated inflammation in lipopolysaccharide-induced RAW264.7 macrophages and significantly augmented chondrogenesis in BMSCs cocultures. Implanting BMSCs-loaded GelMA@G5-Dic/Sr hydrogels in immunocompetent rabbits for 2 and 6 weeks revealed diminished inflammation and enhanced cartilage formation compared to GelMA, GelMA@G5, GelMA@G5-Dic, and GelMA@G5/Sr hydrogels. Collectively, this study introduces an innovative strategy to advance cartilage regeneration by temporally modulating inflammation and chondrogenesis in immunocompetent animals. Through the development of a platform addressing the temporal modulation of inflammation and the limited chondrogenic capacity, we offer valuable insights to the field of cartilage tissue engineering.
Assuntos
Condrogênese , Dendrímeros , Diclofenaco , Inflamação , Nanopartículas , Estrôncio , Condrogênese/efeitos dos fármacos , Estrôncio/química , Estrôncio/farmacologia , Animais , Diclofenaco/farmacologia , Diclofenaco/química , Dendrímeros/química , Dendrímeros/farmacologia , Nanopartículas/química , Inflamação/tratamento farmacológico , Coelhos , Camundongos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Hidrogéis/química , Hidrogéis/farmacologia , Propriedades de Superfície , Gelatina/química , Cartilagem/efeitos dos fármacos , Cartilagem/fisiologia , Liberação Controlada de Fármacos , Engenharia Tecidual , Portadores de Fármacos/químicaRESUMO
OBJECTIVES: To explore the antimicrobial potential of strontium (Sr)-functionalized wafers against multiple bacteria associated with per-implant infections, in both mono- and multispecies biofilms. MATERIALS AND METHODS: The bactericidal and bacteriostatic effect of silicon wafers functionalized with a strontium titanium oxygen coating (Sr-Ti-O) or covered only with Ti (controls) against several bacteria, either grown as a mono-species or multispecies biofilms, was assessed using a bacterial viability assay and a plate counting method. Mono-species biofilms were assessed after 2 and 24 h, while the antimicrobial effect on multispecies biofilms was assessed at Days 1, 3, and 6. The impact of Sr functionalization on the total percentage of Porphyromonas gingivalis in the multispecies biofilm, using qPCR, and gingipain activity was also assessed. RESULTS: Sr-functionalized wafers, compared to controls, were associated with statistically significant less viable cells in both mono- and multispecies tests. The number of colony forming units (CFUs) within the biofilm was significantly less in Sr-functionalized wafers, compared to control wafers, for Staphylococcus aureus at all time points of evaluation and for Escherichia coli at Day 1. Gingipain activity was less in Sr-functionalized wafers, compared to control wafers, and the qPCR showed that P. gingivalis remained below detection levels at Sr-functionalized wafers, while it consisted of 15% of the total biofilm on control wafers at Day 6. CONCLUSION: Sr functionalization displayed promising antimicrobial potential, possessing bactericidal and bacteriostatic ability against bacteria associated with peri-implantitis grown either as mono-species or mixed in a multispecies consortium with several common oral microorganisms.
Assuntos
Biofilmes , Peri-Implantite , Porphyromonas gingivalis , Estrôncio , Titânio , Titânio/química , Titânio/farmacologia , Biofilmes/efeitos dos fármacos , Peri-Implantite/microbiologia , Peri-Implantite/tratamento farmacológico , Estrôncio/farmacologia , Porphyromonas gingivalis/efeitos dos fármacos , Humanos , Antibacterianos/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Materiais Revestidos Biocompatíveis/química , Viabilidade Microbiana/efeitos dos fármacos , Implantes Dentários/microbiologiaRESUMO
Infection and aseptic loosening caused by bacteria and poor osseointegration remain serious challenges for orthopedic implants. The advanced surface modification of implants is an effective strategy for addressing these challenges. This study presents a "pneumatic nanocannon" coating for titanium orthopedic implants to achieve on-demand release of antibacterial and sustained release of osteogenic agents. SrTiO3 nanotubes (SrNT) were constructed on the surface of Ti implants as "cannon barrel," the "cannonball" (antibiotic) and "propellant" (NH4HCO3) were codeposited into SrNT with assistance of mussel-inspired copolymerization of dopamine and subsequently sealed by a layer of polydopamine. The encapsulated NH4HCO3 within the nanotubes could be thermally decomposed into gases under near-infrared irradiation, propelling the on-demand delivery of antibiotics. This coating demonstrated significant efficacy in eliminating typical pathogenic bacteria both in planktonic and biofilm forms. Additionally, this coating exhibited a continuous release of strontium ions, which significantly enhanced the osteogenic differentiation of preosteoblasts. In an implant-associated infection rat model, this coating demonstrated substantial antibacterial efficiency (>99%) and significant promotion of osseointegration, along with alleviated postoperative inflammation. This pneumatic nanocannon coating presents a promising approach to achieving on-demand infection inhibition and sustained osseointegration enhancement for titanium orthopedic implants.